The role of oxygen in regulating microRNAs that control the placental renin-angiotensin system
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE121593 | GEO | 2018/11/30
REPOSITORIES: GEO
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Project description:The placental renin-angiotensin system (RAS) is important for placentation. RAS expression is greatest in early gestation. This may be due (in part) to suppression of miRNAs that target the placental RAS, but this has never been explored. In this study, human placental miRNAs were measured at 10–11 (early), 14–18 (mid), and 38–40 (term) weeks gestation, as well as in placentae from women with early- or late-onset preeclampsia (n=4/group), using an Agilent miRNA microarray (V19). All miRNAs showed a gestational increase and could influence the transgestational profile of the human placental RAS. Additionally, on the array, three miRNAs predicted to target the RAS (miR-892c-3p, miR-378c and miR-514-3p ) were overexpressed in placentae of late-onset preeclamptic women.
2018-08-21 | GSE109832 | GEO
Project description:During early human placental development, extravillous cytotrophoblasts (EVT) invade the uterine vasculature to sequester a maternal blood supply. The impact of this on placental gene expression has not been established for normal pregnancy. Using RNA sequencing, we profiled placental chorionic villous tissues from 96 pregnancies at 6-23 weeks of gestation. We identified 1,048 genes that were differentially expressed between 6-10 weeks’ and 11-23 weeks’ of gestation. These are predominantly genes that are enriched in transcription factor signalling, inflammatory response and cell adhesion. Using a co-expression network and gene set enrichment analyses, we reveal three distinct phases of gene expression coincident with phases of maternal blood flow to the placenta that impact immune function and are likely driven by oxygen tension, potentially in a sex-specific manner. These data represent a comprehensive transcriptional profile of early placental development and point to significant environmental, genetic and regulatory triggers that drive gene expression.
2022-04-20 | GSE150830 | GEO
Project description:Cell-to-cell communication is essential for the spiral artery (SpA) remodeling and required for maternal transfer of nutrient and oxygen to the fetus. Extravillous trophoblast invade the uterine arteries to remodel the SpA during the first 20 weeks of gestation. Interestingly, oxygen tenstion in the uterine environment changes with the progression of pregnancies and damage in the SpA remodelling can lead to preeclampsia and pther pregnancy complications. Recently, our understanding of how cells communicate has undergone a paradigm shift since the recognition of the role of exosomes on intercellular signaling. Here, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT), modifying their bioactivity on endothelial cells. Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on endothelial cells. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly hifger in EVT culturedunder 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, while exosomes from 1% oxygen decrease EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of uniques miRNA in exosomes from EVT cultured at 1% oxygen and exosomes isolated from maternal at early gestation, who developed PE and SPTB later in pregnancy. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically useful biomarker of pregnancy complications.
2017-06-14 | GSE93020 | GEO
Project description:Pancreatic β-cell function impairment is a key mechanism for developing gestational diabetes mellitus (GDM). Maternal and placental exosomes regulate maternal and placental responses during hyperglycemia. Studies have associated exosomal micro RNAs (miRNAs) with GDM development. To date, no studies have been reported that evaluate the profile of miRNAs present in maternal and placental exosomes in the early stages of gestation from pregnancies that develop GDM. We used microarrays to assess whether early pregnancy maternal and placental exosomal miRNA profiles vary according to pancreatic β-cell function in women who will develop GDM (preGDM).
2024-02-29 | GSE243374 | GEO
Project description:This study investigates the processes of angiogenesis and lymphangiogenesis in an in vitro mouse Embryoid Body (EB) model while maintaining as closely as possible an in vivo environment that is observed in human and murine placental development. Several studies have documented that human placental development is profoundly influenced by oxygen tension. Further the developing murine embryo also experiences hypoxic conditions prior to parturition, which regulates early organogenesis and embryonic blood vessel formation in vivo. Embryonic stem (ES) cells derived from 129/SvJ mice were differentiated into embryoid bodies (EBs) and were subjected to two oxygen treatments: normoxia (21% O2) and hypoxia (2.6%). Hypoxia was achieved in a humidified chamber flushed with 95% N2/5% CO2 until the oxygen level was stably maintained at 2.6%. EBs were transferred on days E8, E12, E15 and E18 to hypoxia or maintained in normoxia. After 2 days of differential oxygen treatments, these EBs were analyzed at E10, E14, E17 and E20 respectively.
2012-08-12 | GSE17613 | GEO
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. RNA from cytotrophoblast from 2 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were run on the Illumina HT-12v4 Expression Array
2013-01-18 | E-GEOD-41331 | biostudies-arrayexpress
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. DNA from 2 cell types from 5 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were bisulfite converted and run on the Illumina HumanMethylation450 BeadChip
2013-01-18 | E-GEOD-41336 | biostudies-arrayexpress
Project description:microRNAs are increasingly seen as important regulators of placental development and opportunistic biomarker targets. We generated miRNA profiles using 96 placentas from presumed normal pregnancies, across early gestation, in combination with matched profiles from maternal plasma. We identified 637 miRNAs with expression in 86 samples (after removing poor quality samples), showing a clear gestational age gradient and identified 374 differentially expressed (DE) miRNAs across a gestational cut-off of 6-10 weeks’ and 11-23 weeks’. We see a clear gestational age group bias in miRNA clusters C19MC, C14MC, miR-17~92 and paralogs, regions that also include many DE miRNAs. Proportional change in expression of placenta-specific miRNA clusters was reflected in maternal plasma, with C19MC miRNAs miR-516b-5p and 517a-3p showing potential as a biomarkers. Chorionic villous samples across early gestation display differential miRNA profiles, particularly in the expression of highly placenta-specific miRNA clusters, and at the presumed introduction of oxygenated maternal blood into the placenta. Data presented here comprise a clinically important reference set for studying early placenta development and enabling development of minimally invasive methods for monitoring placental health.
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2022-05-20 | PXD033289 | Pride
Project description:Spontaneous preterm birth (PTB) is a major obstetrical problem around the globe and the mechanisms leading to PTB are unclear. Recently, changes in the circulating levels of placental extracellular vesicles (EVs) during pregnancy have been associated with various pregnancy complications. However, progress in the field is hindered by the inability to isolate placental EVs from the maternal circulation. A longitudinal study design was used to determine the protein cargo present in circulating placental EVs in maternal plasma of term and preterm birth across gestation (i.e. first, second and third trimester). Placental derived EVs were enriched from the total EVs population based on their expression of membrane bound placental alkaline phosphatase (PLAP). A quantitative, information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]) approach identified and quantified the placental EV protein contents. PLAP+ EVs do not change in characteristics (size shape and markers) but did differ in numbers across gestation with low levels in PTB. A comparison analysis between the PLAP+ EV proteome from term and PTB revealed 96 proteins differing significantly (P<0.05, False Discovery Rate 1%) across gestation. Bioinformatics analysis of differentially expressed proteins revealed consistent upregulation of inflammatory pathways in both, upregulation of epithelial mesenchymal transition pathways at term and down regulation of coagulation/complement activation in preterm. Characterization of the proteomic profile in PLAP+ EVs across gestation demonstrates dramatic changes, which might be used to understand the biological process associated with early parturition and develop biomarkers for predicting high risk status for PTB.
2019-11-04 | MSV000084533 | MassIVE